A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
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DOI：
10.1038/s41586-019-0989-6
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发表时间：
2019-03-14
期刊：
影响因子：
64.8
通讯作者：
Chagin, Andrei S.
中科院分区：
文献类型：
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作者：
Newton, Phillip T.;Li, Lei;Chagin, Andrei S.
儿童的纵向骨生长由生长板维持，生长板是软骨的狭窄圆盘，为软骨内骨化提供持续的软骨细胞供应（1）。然而，目前还不清楚这种供应是如何在整个儿童成长过程中保持的。静止区的软骨祖细胞被认为是逐渐消耗的，因为它们为纵向生长提供细胞（1，2），但这种模型从未得到证实。在这里，使用克隆遗传跟踪与多色报告和功能扰动，我们表明，在胎儿和新生儿时期的纵向增长涉及消耗的软骨祖细胞，而在以后的生活中，符合形成的次级骨化中心，软骨祖细胞获得自我更新的能力，从而形成大的，稳定的单克隆柱的软骨细胞。同时，软骨祖细胞开始表达干细胞标志物并进行对称细胞分裂。自我更新祖细胞库的调节涉及雷帕霉素复合物1（mTORC 1）信号通路的刺猬和哺乳动物靶。我们的研究结果表明，干细胞龛发展出生后在骺生长板，这提供了一个持续供应的软骨细胞在一个较长的时间。
Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification(1). However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth(1,2), but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.